U.S. patent number 4,517,173 [Application Number 06/385,647] was granted by the patent office on 1985-05-14 for mucous membrane-adhering film preparation and process for its preparation.
This patent grant is currently assigned to Nippon Soda Co. Ltd.. Invention is credited to Norimasa Fujiyama, Akinori Ito, Hidenori Kizawa, Jitsuo Kobayashi.
United States Patent |
4,517,173 |
Kizawa , et al. |
May 14, 1985 |
Mucous membrane-adhering film preparation and process for its
preparation
Abstract
A mucous membrane-adhering film preparation wherein the film
consists of two layers. One layer of the film consists of the
pharmaceutical agents and water-soluble high polymer material. The
other layer of the film material consists of poor water-soluble
agents. The pharmaceutical agent and water-soluble high polymer
material layer first layer and the poor water-soluble agents second
layer are separately prepared in solvents. The first solution is
coated on a base plate having a favorable releasing nature, and, by
removing the solvent, the film is produced on the base plate, the
second solvent is then coated on the first layer and by removing
the solvent, the desired film having one poor water-soluble surface
is produced.
Inventors: |
Kizawa; Hidenori (Tokyo,
JP), Fujiyama; Norimasa (Tokyo, JP),
Kobayashi; Jitsuo (Kanagawa, JP), Ito; Akinori
(Niigata, JP) |
Assignee: |
Nippon Soda Co. Ltd. (Tokyo,
JP)
|
Family
ID: |
15116781 |
Appl.
No.: |
06/385,647 |
Filed: |
May 25, 1982 |
PCT
Filed: |
September 25, 1981 |
PCT No.: |
PCT/JP81/00254 |
371
Date: |
May 25, 1982 |
102(e)
Date: |
May 25, 1982 |
PCT
Pub. No.: |
WO82/01129 |
PCT
Pub. Date: |
April 15, 1982 |
Foreign Application Priority Data
|
|
|
|
|
Sep 26, 1980 [JP] |
|
|
55/33947 |
|
Current U.S.
Class: |
424/435 |
Current CPC
Class: |
A61K
9/006 (20130101); A61L 26/0023 (20130101); A61L
26/0066 (20130101); A61L 26/0076 (20130101); A61L
26/0023 (20130101); C08L 1/26 (20130101); A61L
2300/204 (20130101); A61L 2300/602 (20130101); A61L
2300/222 (20130101); A61L 2300/412 (20130101) |
Current International
Class: |
A61K
9/00 (20060101); A61L 26/00 (20060101); A61L
015/03 (); A61F 013/00 (); A61K 009/70 () |
Field of
Search: |
;424/16,28 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
|
|
|
|
|
|
|
822075 |
|
Sep 1969 |
|
CA |
|
0040862 |
|
Dec 1981 |
|
EP |
|
45-37038 |
|
Nov 1970 |
|
JP |
|
52-18813 |
|
Feb 1977 |
|
JP |
|
55-62014 |
|
May 1980 |
|
JP |
|
56-100714 |
|
Aug 1981 |
|
JP |
|
56-140927 |
|
Nov 1981 |
|
JP |
|
58-59910 |
|
Apr 1983 |
|
JP |
|
Primary Examiner: Rose; Shep K.
Attorney, Agent or Firm: Oujevolk; George B.
Claims
What is claimed is:
1. A mucous membrane-adhering film preparation with a flat contact
side so formed as to be applied to an oral cavity and to adhere
onto a mucous membrane, said preparation consisting of at least
three layers, namely, a pharmaceutical layer (a), a poor
water-soluble layer (b), and an intermediate layer (c),
wherein:
(a) said pharmaceutical layer (a) is a material selected from the
group consisting of predonisolone and allantoin together with
water-solluble cellulose derivatives selected from the group
consisting of hydroxypropyl cellulose, methyl cellulose, hydroxy
propyl methyl cellulose and mixtures thereof, as a thin film
base;
(b) said poor water-soluble layer (b) consists of water-soluble
cellulose derivative together with poor-water-soluble components,
said components being selected from the group consisting of
shellack, higher fatty acids, and mixtures thereof; and,
(c) said intermediate layer consists of water-soluble cellulose
derivatives not containing a pharmaceutical agent and
not-containing poor water-soluble components.
2. A preparation as claimed in claim 1 wherein the water-soluble
cellulose derivatives are selected so as to have superior film
moldability so as to produce a soft flexible film and the
hydroxypropyl cellulose, methyl cellulose, hydroxy propyl methyl
cellulose and mixtures thereof are so selected as to gradually
discharge the effective components in the mouth.
Description
BACKGROUND OF THE INVENTION
The present invention relates to a preparation which is applied to
a mucous membrane and more particularly it relates to a mucous
membrane-adhering film preparation which is placed on and adheres
onto a mucous membrane part or an inflammed body portion of a
mucous membrane to obtain general or local curing effects, and to a
process for its preparation.
BRIEF DESCRIPTION OF THE PRIOR ART
Preparations used for applying onto a mucous membrane have become
particularly attractive in recent years and give the expectation of
quick curing effects by reason of a high concentration of a
pharmaceutical agent being absorbed by the mucous membrane and
carried directly to the whole body by the body circulatory system,
and, these preparations have a lesser loss of the pharmaceutically
effective component where the loss occurs by decomposition and
chemical or microorganism reactions of the pharmaceutically
effective component with the pH condition, digestive juices and
microorganisms in the gastric and intestinal organs, such as
generally used oral drugs of which the pharmaceutical effective
component is absorbed by a gastric wall and the intestinal organs
and carried to the whole body after passing through the portal
veins and heptic organ.
Troches, buccal tablets, and tongue tablets as preparations for
being applied to a mucous membrane in the oral cavity, a
suppository, vaginal suppository for use in the rectum and vagina,
and an ointment and an adhering tablet as an external preparation
applied directly to the inflammed portion are well known as
preparations to be applied to the mucous membrane.
However, taking preparations for external use as an example, it is
difficult to coat the desired body part alone with the ointment,
particularly in the buccal cavity, the staying time of the
pharmaceutical component on an ulcerated body part is short because
of saliva and the movement of the tongue and cheeks, and the
pharmaceutical effect is small in comparison with the amount of
dosage and this is a serious drawback. Further, the adhering tablet
applied to a larger ulcer stimulates and increases contact pain and
furthermore in the event of applying the tablet to several
ulcerated parts, several pieces of adhering tablets must be placed
on these ulcerated parts and thereby a high pressure of extraneous
material is felt on the body parts.
As preparations to overcome these drawbacks, a preparation of the
type to adhere to the mucous membrane in the oral cavity or nasal
cavity was proposed at the 99th annual meeting of the Japan
Pharmaceutical Society (Aug. 28, 1979) and disclosed in the Public
Bulletin of Japan Open Patent Publication No. 100714/1981 in which
the base agent of the ointment is eccentrically placed in a mucous
membrane-adhering coating layer such as cellulose ether.
This preparation has an improved soft flexibility as compared with
the conventional adhering tablet, but the size of the preparation
is limited.
The present inventors carried out research as to preparations to be
applied to the mucous membrane and as a result they have discovered
a film preparation which comprises at least two layers: (a) a
water-soluble layer containing a pharmaceutical agent, and (b) a
poor water-soluble layer; and, wherein the water-soluble layer is
to be adhered onto the mucous membrane, and thus, the present
invention came into being.
OBJECTS OF THE INVENTION
Therefore, an object of the present invention is to provide a
mucous membrane-adhering film preparation which is improved over
the defects of the prior art.
Another object of the invention is to provide a process for
producing this film preparation.
SUMMARY OF THE INVENTION
Generally speaking, the present invention contemplates a mucous
membrane-adhering film preparation which is to be adhered at the
side of a pharmaceutical layer onto a mucous membrane, which
consists of two layers: (a) a pharmaceutical layer, and (b) a poor
water-soluble layer. The pharmaceutical layer (a) consists mainly
of pharmaceutical agents and water-soluble high polymers as a film
base. The poor water-soluble layer (b) consists mainly of
water-soluble high polymers and agents which have poor
water-soluble characteristics.
The pharmaceutical agent used herein comprises medical agents or
animal agents which can be applied to a mucous membrane or to an
inflamed part on a mucous membrane and cures therapeutically or
prevents a disease in a whole body or in a local portion. Further
it can be used with a pharmaceutical agent which can be dissolved
or dispersed in water or organic solvents at room temperature, and,
the pharmaceutical agent is preferably chosen from those agents
which are discharged gradually whereby a lengthy therapeutical
effect can be expected.
Useful pharmaceutical agents contemplated herein include
predonisone, predonisolone, predonisolone acetate, hydrocortisone,
triamcinolone, dexamethasone, and betamethasone as
anti-inflammatory steroids; aspirin, aminopyrin, acetoaminophen,
ibufenac, ibuprofen, indomethasine, colehicine, sulpyrine,
mephenamic acid, phenacetin, phenylbutazone, fulfenamic acid and
probenecid as anti-inflammatory anodynes and (.alpha.)-chymotrysin
as anti-inflammatory enzymes. Further, it comprises anti-histamine
agents such as diphenhydramine-hydrochloride, and chlorophenylamine
maleate, oral sterilizing agents such as chlorohexydine-
hydrochloride, cetylpyridinium-chloride, hexylresorcin and
nitrofurazone, antibiotic material such as penicillin or its
derivative, cephaphalosporin derivative, erythromycine,
tetracycline hydrochloride, furadiomycin, and leucomycin,
chemically therapeutic agents such as sulfamethyzole and nalidixic,
cardiac strengthening agents such as digatalis and digoxin, blood
vein dilating agents such as nitroglycerine and
papaverine-hydrochloride, local narcotic agents such as lidocain
and procaine-hydrochloride, cough curing agents such as codeine
phosphate and bisorlvon, digesting organ curing agents such as
azulene, phenovalin, pepsin and vitamin U, enzymes such as
lysozyme-chloride or trypsin and antidiabetic agents such as
insulin. Furthermore, it comprises other kinds of agents such as
depressing blood pressure agents, tranquilizers, styptic agents,
sexual hormones and agents for curing virulent carcinoma or
ulcers.
The water-soluble high polymer in the present invention is used for
a film base material producing the film preparation and it
comprises a natural or synthetic water-soluble high polymer having
a superior film moldability and does not give a pharmaceutically
undesired influence to the human body or animal body, but is able
to produce a soft flexible film.
For example, it can be a water-soluble cellulose derivative such as
hydroxypropyl cellulose (hereinafter abbreviated as "HPC"), methyl
cellulose, hydroxypropyl alkylcellulose, carboxymethyl cellulose or
its salt. Further it comprises an acrylic acid copolymer or its
sodium, potassium or ammonium, salt which is obtained by a
copolymerization with poly-acrylic acid or its sodium, potassium
salt or ammonium salt as a main component and methacrylic acid,
styrene or vinyl type of ether (i.e., methyl vinylether or the
like) as a comonomer, poly vinyl alcohol, poly vinyl pyrrolidone,
polyalkylene glycol, hydroxy propyl starch, alginic acid or its
salt, poly-saccharides or those derivatives such as tragacanth, gum
gelatine, collagen or denatured gelatin and collagen treated with
succinic acid or anhydrous phthalic acid.
As the water-soluble high polymer, one or two or more of the
foregoing high polymers may be used, but cellulose derivatives
having superior film moldability and producing the soft flexible
film are preferably used, and also, "HPC" of the numerous cellulose
derivatives, which discharges gradually the effective component is
most desired.
In the invention, the mucous membrane-adhering film preparation
comprises a high polymer film feeding the poor water-soluble layer
onto the single surface of the water-soluble high polymer film,
wherein the single surface of the water-soluble high polymer film
can be poor water-solubilized by using a process of coating a poor
water-soluble layer which is prepared bu adding agents which are
poor in water solubility as the poor water-soluble components to a
water-soluble high polymer onto the single surface of the
water-soluble high polymer film or, a process of partially
crosslinking the single surface of the water-soluble high polymer
film with an irradiation step or radiation ray or an infrared ray.
The process hereinbefore mentioned can be easily carried out and
will not cause the denaturing of the pharmaceutical agent, so that
it is preferably used.
As agents to be used as the poor water-soluble component which is
used by feeding the poor water soluble component to the
water-soluble high polymer film, there are: Shellac, higher fatty
acids including stearic acid and palmitic acid or the like, and
poorly water-soluble cellulose derivatives including ethyl
cellulose, cellulose acetate and butyl cellulose can be used by
applying these components to the single surface of the
water-soluble high polymer film.
The mucous membrane-adhering film preparation of the invention is a
pharmaceutical film preparation in which the single surface of the
water-soluble high polymer film containing the pharmaceutical agent
is treated with the poor water-soluble layer by the process herein
described.
The film preparation is a pharmaceutical preparation for
application to the mucous membrane in which the film preparation is
cut to a desirable size in accordance with the affected diseased
body part and a dosage amount of pharmaceutical component, and, it
is used by plaster adhesive on the mucous membrane in an oral
cavity, nasal cavity, rectum and vagina and thereby a general
and/or local therapeutic effect is obtained.
If desired, a plasticizer, a bulking agent, a taste modifying
agent, an odor modifying agent and a pigment may be added as
additives to the film preparation contemplated herein.
The plasticizer employed for the purpose of appropriately feeding
soft flexibility to the film preparation can be polyethylene glycol
(macrogol), propyleneglycol, glycerine, copolymer with ethylene
oxide and propylene oxide, spun type of fatty acid-lauric ether or
an adduct compound which is obtained by adding ethylene oxide or
propylene oxide to a compound containing an active hydrogen atom
such as sugar cane, sorbitol, glycerine or pentaerythritol. The
polyethylene glycol (macrogol) is preferably used when employing
"HPC" as the water-soluble high polymer.
As the bulking agent, an agent added to conventional tablets is
used such as avicel, mannitol, lactic sugar, sorbitol dextrin,
starch, anhydrous calciumphosphate or amylose.
As a taste modifying agent, organic acid compounds for sour taste
such as citric acid, tartaric acid, fumaric acid or the like, and
sweetening agents such as saccharin, glycyrrhizin or the like and
menthol are used.
As an odor modifying agent, a natural or synthetic perfume agent is
used. As a pigment, an edible pigment added to conventional tablets
is used.
The mucous membrane-adhering film preparation is produced by the
following process:
A clear or suspending solution containing one or two kinds or more
of said pharmaceutical agent and one or more of said water-soluble
high polymer is blended with one or two or more kinds of additives
and thereby the first solution (A) is prepared.
A clear or suspending solution containing one or two or more kinds
of the agents to be the poor water-soluble component and one, two
or more of the water-soluble high polymer is, if desired, blended
with one kind or more of said additives and solution (B) is
prepared.
The solvents for these solutions (A) and (B) selected, depend on
the kind of water-soluble high polymer, pharmaceutical agents,
which are to be the poor water-soluble component, and the additives
and these concentrations. Water, methanol, ethanol, isopropanol,
acetone, methylene chloride and cellusolve or the like may be used
or two kinds of these solvents may be used, taking into
consideration the volatility of the solvent used. If a control for
the residual solvent in the pharmaceutical preparation is taken
into consideration, water and/or ethanol are desirably used.
In the event of preparing said solution (B) by using for example,
the "MPC" as the water-soluble high polymer, an amount of the agent
to be the poor water-soluble component is chosen by weight ratio of
MPC/shellack, in the range of 9/1 to 1/9 and the weight ratio of
MPC/higher fatty acid in a range of 9/1 to 7/3, and the weight
ratio may be optionally chosen by considering a desirable degree of
the water-solubility factor.
The solution (A) and the solution (B) as hereinbefore described is
coated on a base plate having a favorable releasing nature, for
example, a teflon plate or a glass plate, and then, by removing the
solvent, a first film is produced, then another material out of
solutions (A) and (B) is coated on the single surface of the first
film and the solvent is removed, and thereby, the film preparation
having a poor water-soluble surface can be produced. The coating
procedure of the solution (A) or the solution (B) on the base plate
or the prior coated film can be carried out by a brush coating step
or an atomizing spray step. But, by setting a frame mold on the
base plate and pouring the solution into the frame mold, the
thickness of the film can be easily adjusted in a simple and
desirable operation.
Removal of the solvent after the coating step is carried out by
heating the coated membrane under atmospheric pressure or a reduced
pressure.
The film preparation having an optional thickness can be produced
by the foregoing process and the film preparation having a total
thickness of 1 mm or less does not give an extraneous material
sensation when it is placed or made to adhere to the effected
mucous membrane. The poor water-soluble layer in the film
preparation usually has a thickness of 0.01 to 0.9 mm. Also, a
layer which is neither the pharmaceutical agent nor the poor
water-soluble agent may be intermediately inserted between the
layer containing the pharmaceutical agent and the
poor-water-soluble layer. Hereinafter, these are called the
"intermediate layer", the "pharmaceutical agent layer", and the
"poor water-soluble layer".
The invention as well as other objects and advantages thereof will
be better understood from the following detailed description and
the accompanying drawing, in which:
FIG. 1 shows an elution test result of the pharmaceutical agent
from the film preparation which is obtained in the examples
hereinafter described. In the diagram, the ordinate denotes the
elution ratio of the pharmaceutical agent in percentage (%) and the
abscissa denotes elapsed time in minutes. In FIG. 1, "I" marks show
distribution ranges of the elution ratio, and, square marks show
average value of the elution ratio of all samples.
DETAILED DESCRIPTION
Example [1]
(i) Preparation of the film base agent
(a) The solution (A) of the film base agent for preparing the
pharmaceutical layer:
3.5 g of hydropropyl cellulose and 0.5 ml of macrogol-400
(polyethylene glycol) were dissolved in 63 g of ethyl alcohol and
10 ml of distilled water containing 100 mg of dissolved
predonisolone was added to the resulting solution.
(b) The solution (B) for preparing the poor water-soluble
layer:
0.5 g of hydroxypropyl cellulose, 0.25 ml of magrogol (polyethylene
glycol) and 0.25 g of shellac were dissolved in 6 g of ethyl
alcohol.
(c) The solution (C) of the film base agent for preparing the
intermediate layer:
3.5 g of hydroxypropyl cellulose and 0.5 ml of magrogol-400
(polyethylene glycol) were dissolved in 63 g of ethyl alcohol.
(ii) The film molding process
The film base agent solution (A) for producing the pharmaceutical
agent layer (a) was first poured into the film molding frame (i.e.
teflon plate) having 10 cm.sup.2 of surface area, being placed in a
horizontal position. After a drying step, the film base agent
solution (C) for preparing the intermediate layer (c) was poured on
the film containing the pharmaceutical agent and then, after it had
dried, the film base agent solution (B) for preparing the poor
water-soluble layer (b) was injected onto it. After a semi-drying
step, the laminated film was stripped from the film molding frame.
The stripped film was cured at 50.degree. C. temperature for half a
day. The film produced consisted of three layers and had a
transparency and a soft flexibility.
Further, by almost the same operation, three laminated layer films
having different combinations of compositions were obtained as set
forth in Table 1.
Example [2]
Instead of the predonisolone in the film base agent of the
pharmaceutical layer (a) shown in Example [1], allantoin, i.e.
3-ureido hydantoin) was employed. The two laminated films having
different combinations of the composition were obtained from the
film base agent solution (A) containing the allantoin and the film
base agent solution (B) producing the poor water-soluble layer (b)
is set forth in Table 2.
Experimental Example [1]
By using the film preparation in Example [1], an elution test for
the pharmaceutical component "predonisolone" was carried out. The
test result is set forth in FIG. 1.
The Elution Test Apparatus
Product "VSP (NF)" of Toyama Industry Co., Ltd. Standard Grade:
NTR-5S. Aq. Dest. 1,000 ml 37.degree. C. and a basket having 100
rpm rotational velocity.
The Automatic Sampling Apparatus
Product "TAS-30 TC II" of Toyama Industry Co., Ltd. Sampling
amount: 10 ml and interval: 15 minutes.
Experimental Example [2]
The film preparation obtained in Example [1] was applied to a
patient suffering from "After" type of an oral inflammatory
disease. The film preparation is cut to a size slightly larger than
the affected area so that the cut piece may contain from 2 to 16 mg
of predonisolone and the cut piece was made to adhere onto the
affected oral part.
As a result, the film preparation showed favorable adhesive
characteristics and it was not stripped off in the course of its
therapeutical disposal. In all the examples of applying the
invention, a rapid curing effect was recognized.
Further, in using the film preparation of the present invention,
the affected part is protected with a soft film and a physical
stimulus by the teeth or by food can be avoided. Consequently, the
pain which is caused by stress in this disease is greatly
mitigated. As a comparison in this respect, a predonisolone tablet
having 1.2 mm thickness was made to adhere over the affected part
and this time there was a residual pain.
TABLE 1
__________________________________________________________________________
Example No. [1]-1 [1]-2 [1]-3 Poor or Poor or Poor or Pharma-
Difficult Pharma- Difficult Pharma- Difficult ceutical Inter-
water- ceutical Inter- water- ceutical Inter- water- agent mediate
soluble agent mediate soluble agent mediate soluble layer layer
layer layer layer layer layer layer layer
__________________________________________________________________________
Predoni- 100 mg -- -- 100 mg -- -- 100 mg -- -- solone Hydroxy- 3.5
g 3.5 g 0.5 g 3.5 g 2.5 g 0.5 g 3.5 g 2.5 g 0.5 g propyl cellulose
Hydroxy- -- -- -- -- -- -- -- -- -- propyl methyl- cellulose Methyl
-- -- -- -- -- -- -- -- -- cellulose Macrogol 0.5 ml 0.5 ml 0.25 ml
0.5 ml 0.5 ml 0.25 ml 0.5 ml 0.5 ml 0.25 ml 400 Shellac -- -- 0.25
g -- -- 0.25 g -- -- 0.5 g The used 10:0 10:0 10:0 solvent Ethyl
alcohol:
__________________________________________________________________________
[1]-4 [1]-5 Poor or Poor or Pharma- Difficult Pharma- Difficult
ceutical Inter- water- ceutical Inter- water- agent mediate soluble
agent mediate soluble layer layer layer layer layer layer
__________________________________________________________________________
Predoni- 100 mg -- -- 100 mg -- -- solone Hydroxy- 2.0 g 3.5 g 0.3
g 2.0 g 3.5 g 0.3 g propyl cellulose Hydroxy- 1.5 g -- 0.2 g -- --
0.2 g propyl methyl- cellulose Methyl -- -- -- 1.5 g -- --
cellulose Macrogol 0.6 ml 0.5 ml 0.3 ml 0.6 ml 0.5 ml 0.3 ml 400
Shellac -- -- 0.25 g -- -- 0.25 g The used 8.0:2.0 7.0:3.0 solvent
Ethyl alcohol:
__________________________________________________________________________
TABLE 2
__________________________________________________________________________
[2]-1 [2]-2 [2]-3 Poor or Poor or Poor or Difficult Difficult
Difficult Pharmaceutical water-soluble Pharmaceutical water-soluble
Pharmaceutical water-soluble agent layer layer agent layer layer
agent layer layer
__________________________________________________________________________
Allantion 2.0 g 2.0 g 2.0 g Hydroxypropyl cellulose 3.5 g 0.75 g
3.5 g 0.5 g 3.5 g 0.25 g Macrogol 400 1.0 ml 0.25 ml 1.0 ml 0.25 ml
1.0 ml 0.25 ml Shellac -- 0.25 g -- 0.5 g -- 0.75 g The used
solvent Ethyl alcohol Ethyl alcohol Ethyl alcohol
__________________________________________________________________________
INDUSTRIAL UTILIZATION
The mucous membrane-adhering film preparation of the present
invention is a complex film preparation which consists of a
pharmaceutical layer and poor water-soluble layer, or, a
pharmaceutical layer, an intermediate layer and a poor
water-soluble layer. Consequently, the pharmaceutical layer
strongly adheres to the diseased part by absorbing moisture content
and then, the pharmaceutical layer becomes wet and swollen.
Subsequently, the pharmaceutical agent is gradually dissolved in
the diseased part in the course of long hours and the
pharmaceutical agent can then be almost homogeneously eluted.
On the other hand, the poor water-soluble layer has poor water
solubility and consequently, the pharmaceutical component of the
pharmaceutical layer is not eluted and it can be retained in a
buccal cavity or the like for long hours without giving a feeling
of contacting an extraneous material.
As heretofore mentioned, the film preparation indicates a superior
effect which is entirely different from that found in a
conventional pharmaceutical preparation.
The following are features of the film preparation of the present
invention:
(1) The film preparation can be used for therapeutical purposes on
a local diseased part or for the whole body.
(2) Because of the gradual discharge of the pharmaceutical
component, the useful hours are long and less stimulation is given
to the diseased part.
(3) The film preparation can be used for the musous membrane or the
diseased part wetted with a diffused liquid or a secreted
liquid.
(4) The film preparation can be cut to any size and thereby a
predetermined amount of the pharmaceutical agent may be used.
(5) The film preparation protects the diseased part from physical
harm.
(6) many different pharmaceutical agents can be used for the film
preparation.
(7) The film preparation may be provided with an adhesive.
(8) The film preparation has a soft flexibility.
(9) Even if the film base agent is swallowed, it is not absorbed in
the walls of the internal organs.
(10) The film preparation has low toxicity and is safe.
It is to be observed therefore that the present invention provides
a novel film preparation for applying to the mucous membrane and to
the process of producing the preparation.
* * * * *